The goal of this proposal is to determine the feasibility of oral vaccination with recombinant Helicobacter pylori urease. This goal will be tested by the oral immunization of germ and specific pathogen free mice with recombinant urease fusion proteins in formulations designed to elicit mucosal immune responses. The gastric immune response to the vaccination will be confirmed. Protection will be assessed by gastric challenge with H. felis. H. pylori infections of humans have been shown to cause chronic gastritis and peptic ulcer disease. Treatment of these conditions currently involves the use of compounds to reduce stomach acid as well as antibiotic therapies to eradicate the bacterium. These approaches have been met with limited success and recurrence of disease is common. Immunization to prevent infection by these organisms is a novel approach to prevent the occurrence of these diseases rather than reliance on marginally effective treatments. The results of these preliminary experiments will provide a basis for Phase II experiments in non-human primates using direct challenge with H. pylori to confirm the efficacy of vaccination in the prevention gastric.